Optically active dihydrosphingosines, which are obtained by removing the amino group protecting group from optically active dihydrosphingosine derivatives represented by formula (IV): ##STR2## wherein R.sup.3 represents a straight-chain alkyl group having 7 to 21 carbon atoms; and R.sup.4 represents an amino group protecting group (the compound according to the present invention, hereinafter described), are known to be useful as an active ingredient of, for example, dermal preparations for external application (see JP-A-5-85924, the term "JP-A" as used herein means an "unexamined published Japanese patent application"). They are also known as an important constituent of the chemical structures of ceramides having a horny layer moisturizing activity and cerebroside and ganglioside having various biological activities.
Optically active dihydrosphingosines have conventionally been produced by the following processes:
(A) A process comprising optical resolution of racemic dihydrosphingosines. PA1 (B) A process starting with optically active naturally-occurring substances. PA1 (C) A process comprising asymmetric synthesis.
Process (A) involves waste because an unnecessary enantiomer is produced in the same amount as a desired optical isomer.
Process (B) includes the method reported by E. J. Reist, et al. in J. Org. Chem., Vol. 35, p. 3521 (1970), in which an optically active amino sugar is used as a starting material and a Wittig reaction is carried out, and the method reported by T. Hino, et al. in Chem. Lett., p. 1407 (1990), in which L-serine is used as a starting material, and a long-chain alkylene is added thereto, followed by reduction. The former method is impractical due to as low a yield as 30% attained in the Wittig reaction and many steps required; and the latter method is industrially unsuitable because the selectivity to a desired erythro form is only 90% and the starting material L-serine is expensive.
As process (C), W. R. Roush, et al. report in J. Org. Chem., Vol. 50, pp. 3752-3757 (1985) a process comprising a Horner-Emmons reaction of palmitic aldehyde to obtain (2E)-octadec-2-en-1-ol, asymmetric epoxidation of the (2E)-octadec-2-en-1-ol using t-butyl hydroperoxide to obtain an optically active epoxide, reacting the epoxide with sodium hydride to obtain an oxazolidinone derivative, and ring opening to obtain an optically active dihydrosphingosine having 18 carbon atoms. This process is disadvantageous in that highly pure (2E)-octadecan-2-en-1-ol should be prepared in order to obtain an epoxy compound having a high optical purity and that a peroxide, such as t-butyl hydroperoxide, which is an explosive reagent difficult to handle, must be used in quantity.
For preparation of racemic dihydrosphingosines, K. Sisido, et al., report in J. Org. Chem., Vol. 29, No. 9, pp. 2783-2784 (1964) a process comprising, for example, reacting methyl trans-2-octadecenoate with perbenzoic acid in chloroform to obtain methyl 2,3-epoxyoctadecanoate having formula (V'): ##STR3## whose planar structure is the same as that of the compound represented by formula (V) hereinafter described, hydrolyzing the ester (V'), cyclizing the resulting acid by reaction with benzylamine to obtain 2-benzylamino-3-hydroxyoctadecanoic acid (cyclization yield: 68%), converting the acid to a methyl ester, and reducing the ester in an ether solvent with lithium aluminum hydride (LiAlH4) (reduction yield: 71%). Reduction of such a carboxylic acid as 2-benzylamino-3-hydroxyoctadecanoic acid to an alcohol has generally been carried out by once esterifying the carboxylic acid and using LiAlH.sub.4 as a reducing agent as in the above report. However, LiAlH.sub.4 is a reagent unsuitable to industrial use because it is not only expensive but difficult to handle on account of reactivity with moisture in air.
Use of sodium tetrahydroborate (NaBH.sub.4), which is cheaper than LiAlH.sub.4, as a reducing agent for reduction of ethyl 2-amino-3-hydroxy-4-octadecanoate structurally similar to the compound of formula (III) according to the invention (hereinafter described) to an alcohol is also reported in A. S. Cavallo, et al., J. Org. Chem., Vol. 59, No. 11, pp. 3240-3242 (1994). In this case, however, the reaction time is as long as 4 days, and many steps are involved, including esterification of the carboxylic acid prior to reduction as in the case of using LiAlH.sub.4, so that there is a fear of reduction in yield.
Reduction of an amino acid (e.g., L-valine or L-methionine) or an amino acid derivative (e.g., a hydroxyproline derivative) to a corresponding amino-alcohol without esterifying the carboxyl group has been proposed in A. Abiko, et al., Tetrahedron Lett., Vol. 33, No. 38, pp. 5517-5518 (1992) and T. F. Braish, et al., J. Org. Chem., Vol. 55, pp. 1684-1687, in which reduction is effected using NaBH.sub.4 and a Lewis acid catalyst (e.g., boron trifluoride etherate) while generating borane. However, no report is found concerning reduction of such an alkanoic acid that has a chain structure in which an amino-substituted carbon atom adjoins a hydroxyl-substituted carbon atom (for example, a 2-amino-3-hydroxyalkanoic acid of formula (I) used as a starting compound in the invention) by using NaBH.sub.4 without esterification.
Preparation of optically active dihydrosphingosines has thus been attempted in various ways, but none of the proposals made to date is not fully satisfactory in optical purity and suitability to industrial mass production from the standpoint of ease in reagent handling and the number of necessary steps.